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Metabolic suppression of platelet‐type 12‐lipoxygenase in human uterine cervix with invasive carcinoma
Author(s) -
Nigam Santosh,
Kumar G. Sravan,
Sutherland Mark,
Schewe Tankred,
Ikawa Hiroshi,
Yamasaki Yoshikazu,
Ueda Natsuo,
Yamamoto Shozo
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990909)82:6<827::aid-ijc10>3.0.co;2-q
Subject(s) - lipoxygenase , arachidonic acid , enzyme , platelet , biology , immunohistochemistry , western blot , arachidonate 5 lipoxygenase , cervical carcinoma , carcinoma , carcinogenesis , biochemistry , cervical cancer , endocrinology , chemistry , medicine , cancer , immunology , gene
Several types of lipoxygenases with various functions occur in mammalian cells. Although the presence of 12‐lipoxygenase activity has been reported in uterine tissues, neither its type nor its biological functions have yet been established. Moreover, the putative role of uterine 12‐lipoxygenase in cervical cancer has not been addressed before. Homogenates of uterine tissues from women without cancer and from patients with invasive cervical carcinoma were incubated with (1‐ 14 C)‐arachidonic acid under various conditions and the labelled reaction products were analyzed both by thin‐layer chromatography and by high‐pressure liquid chromatography. 12‐Lipoxygenase protein was estimated by Western blot using anti‐serum against recombinant human platelet‐type 12‐lipoxygenase. Highest concentrations and activities of 12‐lipoxygenase were found in the exocervix. The formation of 12S‐hydroxy‐5Z,8Z,10E,14Z‐eicosatetraenoic acid (12‐HETE) was stimulated by micromolar concentrations of 13S‐hydroperoxy‐9Z,11E‐octadecadienoic acid, suggesting metabolic control of the 12‐lipoxygenase activity via the hydroperoxide tone. Immunohistochemical investigation revealed that the enzyme is mainly located in the squamous epithelium, and is of platelet‐type. Significantly lower values for the 12‐HETE formation were found in samples from patients with invasive cervical carcinoma, whereas the amount of immunochemically detectable 12‐lipoxygenase protein was unaltered. At the same time the expression levels of the bcl ‐2 gene were enhanced. Thus, it is concluded that during carcinogenesis the hydroperoxide‐reducing capacity of the uterine cervix tissue is enhanced, possibly mediated by bcl‐2 protein, and in turn metabolically suppresses the 12‐lipoxygenase activity. Furthermore, the data suggest an anti‐carcinogenic action of 12‐lipoxygenase in human cervix, in contrast to its reported pro‐carcinogenic action in breast cancer. Int. J. Cancer 82:827–831, 1999. © 1999 Wiley‐Liss, Inc.